|Study Demonstrates Safety of Oral Contraceptives in Women
In a major study funded by the National Institute of Arthritis and Musculoskeletal
and Skin Diseases (NIAMS), a part of the National Institutes of Health (NIH),
women with either inactive or stable systemic lupus erythematosus (lupus) — a
disease in which the body’s immune system mistakenly attacks and damages healthy
tissues of the skin, joints and internal organs — were able to take oral contraceptives
without increased risk of flares, or periods of increased disease activity, that
characterize the disease.
Safe and effective contraception is an issue that many women of childbearing
age face. But for women with lupus, doctors have often been hesitant to prescribe
one of the most effective forms of contraception — oral contraceptives, or the “pill” — for
fear that it might increase disease activity.
In the 15-center study of 183 women with inactive or stable lupus, those taking
oral contraceptives (triphasic 35 µg.ethinylestradiol/0.5-1 mg norethindrone
for twelve 28-day cycles) had no statistically significant difference in the
occurrence of flares than those taking a placebo. Severe flares occurred in about
7 percent of the women, regardless of whether they received oral contraceptives
or placebo. A severe flare was defined by several criteria, including the presence
of new or worsening central nervous system involvement; inflammation of the blood
vessels (vasculitis), kidneys (nephritis) and/or muscles (myositis); and/or blood
problems, including low platelet count (thrombocytopenia) and destruction of
the red blood cells (hemolytic anemia).
Mild-to-moderate flares and disease complications were similar between the two
groups over the 12-month follow-up as well. Mild-to-moderate flares included
fevers and inflammation of the skin, joints, the sac of fibrous tissue that surrounds
the heart (pericarditis), and mucous membranes lining the nose and mouth.
Reluctance to prescribe oral contraceptives and other hormones for women with
lupus arose in part from the fact that lupus is far more common in women (women
with the disease outnumber men 10 to 1), and that it typically begins during
the childbearing years (after the onset and before the cessation of menstruation)
when female hormone levels are at their peak. In mouse models of lupus, giving
estrogen makes lupus worse and, depending on the genetic background, influences
the activity of white blood cells called B cells that are believed to play a
key role in the disease process.
But for most women with moderate lupus that is inactive or stable, taking estrogen — whether
as part of an oral contraceptive or hormone replacement therapy — appears to
have no detrimental effect on disease activity, say co-authors Jill Buyon, M.D.,
of New York’s Hospital for Joint Diseases, and Michelle Petri, M.D., M.P.H.,
of the Johns Hopkins University, who jointly led the study. However, they note
that oral contraceptives still are not advised for women who have a history of,
or are at high risk for, blood clots, because estrogens have been associated
with dangerous blood clots.
The recently published study on oral contraceptives is one of two separate
randomized, placebo-controlled studies that comprise the Safety of Estrogens
in Lupus Erythematosus, National Assessment (SELENA) Trial. The other study,
which showed no increased risk of severe flares in postmenopausal women on hormone
replacement therapy, was published earlier this year (Buyon JP, et. al. The effect
of combined estrogen and progesterone hormone replacement therapy on disease
activity in systemic lupus erythematosus: a randomized trial,” Ann Intern Med
2005; 142: 953-962).
“There are settings in which estrogens might provide benefit,” say the authors.
Among women with lupus, they say, there is a high elective abortion rate — approaching
23 percent of pregnancies — which may reflect a failure of the birth control
method used or the absence of an adequate birth control program.
“Estrogen, as used in this study, appears to be safe in the majority of women
with stable disease,” says NIAMS Director Stephen I. Katz, M.D., Ph.D. “This
research brings us another step forward in improving quality of life for people
with rheumatic disease.”
In addition to NIAMS, other funders of the study included NIH’s Office of Research
on Women’s Health, National Center on Minority Health and Health Disparities, National Center for
Research Resources and National Institute of Allergy and Infectious Diseases.
The mission of the National Institute of Arthritis and Musculoskeletal and
Skin Diseases (NIAMS), a part of the Department of Health and Human Services’ National
Institutes of Health, is to support research into the causes, treatment, and
prevention of arthritis and musculoskeletal and skin diseases; the training
of basic and clinical scientists to carry out this research; and the dissemination
of information on research progress in these diseases. For additional information,
call NIAMS’s Clearinghouse toll free at 1-877-22-NIAMS, or visit the NIAMS
Web site at www.niams.nih.gov.
The National Institutes of Health (NIH) — The Nation's Medical Research
Agency — includes 27 Institutes and Centers and is a component of
the U. S. Department of Health and Human Services. It is the primary Federal
agency for conducting and supporting basic, clinical, and translational medical
research, and it investigates the causes, treatments, and cures for both common
and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.